Pathologic characteristics of human venous in-stent stenosis and stent occlusion

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ObjectiveThe objective of this study was to determine the pathologic features of venous in-stent stenosis over time occurring in bare metal stents. MethodsEndovascular biopsy samples were obtained prospectively from venous bare metal stents implanted in 2009 through 2018. All samples were formalin-fixed, paraffin-embedded and stained with hematoxylin and eosin. Samples were examined by a cardiovascular pathologist to estimate the amount of its constituent components, which included fresh thrombus, organizing thrombus, old thrombus, or diffuse intimal thickening (DIT), and pathologic features including calcification, neovascularization, and hemosiderin deposition. This pathologic characterization was correlated with time following stent implantation to discern time-dependence of pathologic evolution of in-stent stenosis using both descriptive statistics and binary logistic regression. ResultsA total of 254 post-stent venograms with biopsies of in-stent contents from 148 unique patients were studied. Fresh thrombus and organizing thrombus were both present across all studied time intervals. Old thrombus was seen beginning at approximately 2 weeks and DIT at approximately 4 weeks. Calcification was a rare finding encountered at later time intervals. The prevalence of each component varied with time: the probability of encountering fresh thrombus (P = .010) and organizing thrombus (P = .008) decreased over time. By contrast, the probability of finding DIT (P = .002) and calcifications (P < .001) increased over time. The presence of old thrombus, neovascularization, or hemosiderin did not demonstrate time dependence. Diffuse intimal thickening was frequently seen along with organizing thrombus as well as independently, and in many instances, these two features were directly merged. ConclusionsThe evolution of human venous in-stent restenosis appears to follow a time-dependent course, suggesting a possible progressive evolution from fresh and organizing thrombus to DIT. Contrasted with the literature on arterial in-stent restenosis, vein in-stent restenosis may have an increased thrombus prevalence (both organizing and old thrombus). DIT is a primary feature of late in-stent stenosis and may explain in part why many of these lesions may not respond to thrombolytic or anticoagulant treatment alone.